Jacob Bell
New Member
Medicine in the Western World has forgotten almost all it once knew
about therapeutic properties of marijuana, or cannabis.
Analgesia, anticonvulsant action, appetite stimulation, ataraxia, antibiotic
properties and low toxicity were described throughout medical
literature, beginning in 1839, when O'Shaughnessy introduced cannabis
into the Western pharnacopoeia.
As these findings were reported throughout Western medicine, cannabis
attained wide use. Cannabis therapy was described in most pharmacopoeial
texts as a treatment for a variety of disease conditions.
During the second half of the 1800's and in the present century,
medical researchers in some measure corroborated the early reports
of the therapeutic potential of cannabis. In addition, much laboratory
research has been concerned with bioassay, determination of the mode
of action, and attempts to solve the problems of insolubility in water
and variability of strength among different cannabis specimens.
"Recreational" smoking of cannabis in the twentieth century and the
resultant restrictive federal legislation have functionally ended all medical
uses of marijuana.
In light of such assets as minimal toxicity, no buildup of tolerance,
no physical dependence, and minimal autonomic disturbance, immediate
major clinical reinvestigation of cannabis preparations is indicated
in the management of pain, chronic neurologic diseases, convulsive disorders,
migraine headache, anorexia, mental illness, and bacterial infections.
CANNABIS INDICA, CANNABIS sativa, Cannabis
americanus, Indian hemp and marijuana (or marihuana)
all refer to the same plant. Cannabis is used
throughout the world for diverse purposes and has
a long history characterized by usefulness, euphoria
or evil-depending on one's point of view.
To the agriculturist cannabis is a fiber crop; to
the physician of a century ago it was a valuable
medicine; to the physician of today it is an enigma;
to the user, a euphoriant; to the police, a menace;
to the traffickers, a source of profitable danger; to
the convict or parolee and his family, a source of
sorrow.
This paper is concerned primarily with the medicinal
aspects of cannabis.
Cannabis in Medicine Before 1800
The Chinese emperor Shen-nung is reported to
have taught his people to grow hemp for fiber in
the twenty-eighth century B.C. A text from the
period 1500-1200 B.C. documents a knowledge of
the plant in China-but not for use as fiber. In 200
A.D., the use of cannabis as an analgesic was described
by the physician Hoa-tho.44
In India the use of hemp preparations as a
remedy was described before 1000 B.C. In Persia,
cannabis was known several centuries before
Christ. In Assyria, about 650 B.C., its intoxicating
properties were noted."4
Except for Herodotus' report that the Scythians
used the smoke from burning hemp seeds for intoxication,
the ancient Greeks seemed to be unaware
of the psychoactive properties of cannabis.
Dioscorides in the first century A.D. rendered an
accurate morphologic description of the plant, but
made no note of intoxicating properties.10
In the thirteenth and fourteenth centuries,
Arabic writers described the social use of cannabis
and resultant cruel but unsuccessful attempts to
suppress its non-medical use.44
Although Galen described the use of the seeds
for creating warmth, he did not describe the intoxicating
qualities of hemp. Of interest is the paucity
of references to hemp's intoxicating properties in
the lay and medical literature of Europe before the
1 800'S.44
Cannabis in Nineteenth-Century Medicine
The therapeutic use of cannabis was introduced
into Western medicine in 1839, in a 40-page article
by W. B. O'Shaughnessy, a 30-year-old physician
serving with the British in India.27 His discussion
of the history of the use of cannabis products in the
East reveals an awareness that these drugs had not
only been used in medicine for therapeutic purposes,
but had also been used for recreational and
religious purposes.
O'Shaughnessy is not primarily known for his
discovery of hemp drugs, but rather for his basic
studies on intravenous electrolyte therapy in 1831,
and his introduction of the telegraph into India in
the 1850's.26
After studying the literature on cannabis and
conferring with contemporary Hindu and Mohammedan
wise men, O'Shaughnessy tested the effects
of various hemp preparations on animals, before
attempting to use them to treat humans. Satisfied
that the drug was reasonably safe, he administered
preparations of cannabis extract to patients, and
discovered that it had analgesic and sedative properties.
O'Shaughnessy successfully relieved the pain
of rheumatism and stilled the convulsions of an
infant with this strange new drug. His most spectacular
success came, however, when he quelled
the wrenching muscle spasms of tetanus and rabies
with the fragrant resin. Psychic effects resembling a
curious delirium, when an overdose was given,
were treated with strong purgatives, emetics with a
blister.to the nape of the neck, and leeches on the
temples.27
The use of cannabis derivatives for medicinal
purposes spread rapidly throughout Western medicine,
as is evidenced in the report of the Committee
on Cannabis Indica of the Ohio State Medical
Society, published in 1860. In that report physicians
told of success in treating stomach pain,
childbirth psychosis, chronic cough, and gonorrhea
with hemp products.25 A Dr. Fronmueller, of
Fuerth, Ohio, summarized his experiences with the
drug as follows:
I have used hemp many hundred times to
relieve local pains of an inflammatory as well
as neuralgic nature, and judging from these
experiments, I have to assign to the Indian
hemp a place among the so-called hypnotic
medicines next to opium; its effects are less
intense, and the secretions are not so much
suppressed by it. Digestion is not disturbed;
the appetite rather increased; sickness of the
stomach seldom induced; congestion never.
Hemp may consequently be employed in inflammatory
conditions. It disturbs the expectoration
far less than opium; the nervous
system is also not so much affected. The
whole effect of hemp being less violent, and
producing a more natural sleep, without interfering
with the actions of the internal organs,
it is certainly often preferable to opium, although
it is not equal to that drug in strength
and reliability. An alternating course of
opium and Indian hemp seems particularly
adapted to those cases where opium alone
fails in producing the desired effect.25
Because cannabis did not lead to physical dependence,
it was found to be superior to the opiates
for a number of therapeutic purposes. Birch, in
1889, reported success in treating opiate and
chloral addiction with cannabis,5 and Mattison in
1891 recommended its use to the young physician,
comparing it favorably with the opiates:
With a wish for speedy effect, it is so easy
to use that modern mischief-maker, hypodermic
morphia, that they [young physicians]
are prone to forget remote results of incautious
opiate giving.
Would that the wisdom which has come to
their professional fathers through, it may be,
a hapless experience, might serve them to
steer clear of narcotic shoals on which many
a patient has gone awreck.
Indian hemp is not here lauded as a specific.
It will, at times, fail. So do other drugs.
But the many cases in which it acts well, entitle
it to a large and lasting confidence.
My experience warrants this statement:
cannabis indica is, often, a safe and successful
anodyne and hypnotic.23
In their study of the medical applications of
cannabis, physicians of the nineteenth century repeatedly
encountered a number of difficulties. Recognizing
the therapeutic potential of the drug,
many experimenters sought ways of overcoming
these drawbacks to its use in medicine, in particular
the following:
Cannabis products are insoluble in water.
The onset of the effects of medicinal preparations
of cannabis takes an hour or so; its action is
therefore slower than that of many other drugs.
Different batches of cannabis derivatives vary
greatly in strength; moreover, the common procedure
for standardization of cannabis samples, by
administration to test animals, is subject to error
owing to variability of reactions among the animals.
There is wide variation among humans in their
individual responses to cannabis.
Despite these problems regarding the uncertainty
of potency and dosage and the difficulties in mode
of administration, cannabis has several important
advantages over other substances used as analgesics,
sedatives, and hypnotics:
The prolonged use of cannabis does not lead to
the development of physical dependence.1 '1,131424,
39,44
There is minimal development of tolerance to
cannabis products. * 11,13,14,24,44
Cannabis products have exceedingly low toxicity.
9.21'22'24 (The oral dose required to kill a
mouse has been found to be about 40,000 times the
dose required to produce typical symptoms of intoxication
in man.)21
Cannabis produces no disturbance of vegetative
functioning, whereas the opiates inhibit the gastrointestinal
tract, the flow of bile and the cough
reflex."2'24'44'46
Besides investigating the physical effects of
medicinal preparations of cannabis, nineteenth-century
physicians observed the psychic effects of the
drug in its therapeutic applications.4'27'33 They
found that cannabis first mildly stimulates, and
then sedates the higher centers of the brain. Hare
suggested in 1887 a possible mechanism of cannabis'
analgesic properties:
During the time that this remarkable drug
is relieving pain a very curious psychical condition
manifests itself; namely, that the diminution
of the pain seems to be due to its fading
away in the distance, so that the pain becomes
less and less, just as the pain in a delicate ear
would grow less and less as a beaten drum
was carried farther and farther out of the
range of hearing.
This condition is probably associated with
the other well-known symptom produced by
the drug; namely, the prolongation of time.16
Reynolds, in 1890,33 summed up 30 years of his
clinical experience using cannabis, finding it useful
as a nocturnal sedative in senile insomnia, and
valuable in treating dysmenorrhea, neuralgias including
tic douloureux and tabetic symptoms,
migraine headache and certain epileptoid or choreoid
muscle spasms. He felt it to be of uncertain
benefit in asthma, alcoholic delirium and depressions.
Reynolds thought cannabis to be of no value
in joint pains that were aggravated by motion and
in cases of true chronic epilepsy.
Reynolds stressed the necessity of titrating the
dose of each patient, increasing gradually every
third or fourth day, to avoid "toxic" effects:
The dose should be given in minimum
quantity, repeated in not less than four or six
hours, and gradually increased by one drop
every third or fourth day, until either relief
is obtained, or the drug is proved, in such
case, to be useless. With these precautions I
have never met with any toxic effects, and
have rarely failed to find, after a comparatively
short time, either the value or the uselessness
of the drug.33
Concerning migraine headache, Osler stated in
his text11: Cannabis indica is probably the most
satisfactory remedy.' 1,28
Cannabis in Twentieth-Century Medicine
In his definitive survey of the literature and report
of his own studies, deceptively titled Marihuana,
America's New Drug Problem, Walton
notes that cannabis was widely used during the latter
half of the nineteenth century, and particularly
before new drugs were developed:
This popularity of the hemp drugs can be
attributed partly to the fact that they were introduced
before the synthetic hypnotics and
analgesics. Chloral hydrate was not introduced
until 1869 and was followed in the
next 30 years by paraldehyde, sulfonal and
the barbitals. Antipyrine and acetanilide, the
first of their particular group of analgesics,
were introduced about 1884. For general
sedative and analgesic purposes, the only
drugs commonly used at this time were the
morphine derivatives and their disadvantages
were very well known. In fact, the most attractive
feature of the hemp narcotics was
probably the fact that they did not exhibit
certain of the notorious disadvantages of the
opiates. The hemp narcotics do not constipate
at all, they more often increase than decrease
appetite, they do not particularly depress the
respiratory center even in large doses, they
rarely or never cause pruritus or cutaneous
eruptions and, most important, the liability of
developing addiction is very much less than
with opiates.44
The use of cannabis in American medicine was
seriously affected by the increased use of opiates
in the latter half of the nineteenth century. With
the introduction of the hypodermic syringe into
American medicine from England in 1856 by Barker
and Ruppaner, the use of the faster acting,
water-soluble opiate drugs rapidly increased. The
Civil War helped to spread the use of opiates in
this country; the injected drugs were administered
widely-and often indiscriminately-to relieve the
pain of maimed soldiers returning from combat.
(Opiate addiction was once called the "army
disease".)41 As the use of injected opiates increased,
cannabis declined in popularity.
Cannabis preparations were still widely available
in legend and over-the-counter forms in the 1930's.
Crump* in 1931 mentioned the proprietaries
"Piso's Cure," "One Day Cough Cure" and "Neurosine"
as containing cannabis.44 In 1937 Sasman
listed 28 pharmaceuticals containing cannabis.36
Cannabis was still recognized as a medicinal agent
in that year, when the committee on legislative activities
of the American Medical Association concluded
as follows:
.. . there is positively no evidence to indicate
the abuse of cannabis as a medicinal
agent or to show that its medicinal use is leading
to the development of cannabis addiction.
Cannabis at the present time is slightly used
for medicinal purposes, but it would seem
worthwhile to maintain its status as a medicinal
agent for such purposes as it now has.
There is a possibility that a re-study of the
drug by modern means may show other advantages
to be derived from its medicinal
use.32
Meanwhile, in Mexico, the poor were smoking
marijuana to relax and to endure heat and fatigue.
(Originally Marijuana was the Mexican slang word
for the smoking preparation of dried leaves and
flowering tops of the Cannabis sativa plant-the
indigenous variety of the hemp plant.)
The recreational smoking of marijuana may
have started in this country in New Orleans in
about 1910, and continued on a small scale there
until 1926, when a newspaper ran a six-part series
on the use of the drug.44 The fad subsequently
spread up the Mississippi and throughout the
United States, faster than local and state laws
could be passed to discourage it. The use of "tea"
or "muggles" blossomed into a minor "psychedelic
revolution" of the 1930's. Narcotics officers encouraged
the enactment of local prohibitory laws
and eventually succeeded in bringing about restrictive
Federal legislation. In 1937 Congress passed
the Marihuana Tax Act, the finale to a series of
prohibitory acts in the individual states. Under the
new laws, the already dwindling use of cannabis
as a therapeutic substance in medicine was brought
to a virtual halt. In 1941, cannabis was dropped
from the National Formulary and Pharmacopoeia.
Around the time of the passage of the Marihuana
Tax Act, Walton postulated sites of action
for cannabis drugs. Cortical areas, he found, are
affected at low dosage, while at high dosage there
seems to be a depressant effect on the thalamocortical
pathways. Hyperemia of the brain appears
to be a local phenomenon, unless centers controlling
vasodilation might be located in the
thalamo-cortical region. Similar possible mechanisms
are suggested for the phenomenon of mild
hypoglycemia, usual hunger and thirst and occasional
lacrimation and nausea.44
Despite restrictive legislation, a few medical researchers
have had the opportunity to continue the
investigation of the therapeutic applications of cannabis
in recent years. In his study of the medical
applications of cannabis for Mayor LaGuardia's
committee, Dr. Samuel Allentuck reported, among
other findings, favorable results in treating withdrawal
of opiate addicts with tetrahydrocannabinol
(THC), a powerful purified product of the hemp
plant.1.24
An article in 1949, buried in a journal of chemical
abstracts, reported that a substance related to
THC controlled epileptic seizures in a group of
children more effectively than diphenylhydantoin
(Dilantin®), a most commonly prescribed anticonvulsant.
9
A number of experimenters, believing that cannabis
products might be of value in psychiatry,
have investigated the applications of various forms
of them in the treatment of mental disorders. Cannabis
had been used in the nineteenth century to
treat mental illness.19.25.45.46 However, aside from
some rather equivocal clinical studies, primarily in
the treatment of depression,29.30 35.39 and another
report of success in treating withdrawal from
alcohol and opiate addiction,42 no significant contemporary
psychiatric studies involving cannabis
therapy have been reported to date.
The Current Status of Cannabis Research
Many current "authoritative" publications unequivocally
state that there is no legitimate medical
use for marijuana. As compared with the
1800's, this century has seen very little medical
research on the array of some 20 chemicals that
are found in the hemp plant.37
Today's readers may tend to be skeptical about
a report of a cure for gonorrhea published over a
century ago.19.25 Such findings may bear reinvestigation,
however, in the light of a report from
Czechoslovakia in 1960 that cannabidiolic acid, a
product of the unripe hemp plant, has bacteriocidal
properties.7 Some of the therapeutic applications
reported in the early medical papers have been
corroborated by later investigators, but for the
most part the therapeutic aspects of cannabis remain
to be re-explored under modern clinical
conditions.
In the past 20 years, clinical and basic research
on cannabis have dwindled to practically nothing.
The record of tax stamps issued by the Federal
Bureau of Narcotics for cannabis research, as compared
with those for research on narcotic drugs,
tells the story of the 20-year "drought" in the investigation
of cannabis products: 43 Eleven studies funded by the National Institute
of Mental Health in 1967 concerning cannabis
were either specialized animal experiments, part of
an observational sociologic study of a number of
drugs, or explorations of chemical detection
methods.
The Future of Cannabis and Medicine
Unless existing restrictive state and Federal laws
governing marijuana are changed, there will be no
future for either modern scientific investigation or
controlled clinical trial by present-day methods.
A concerted effort is indicated for full-scale
investigations where knowledge is lacking. Acute
and chronic effects of cannabis should be restudied
by modern methods. Metabolic pathways of action
and detoxification need exploration by the pharmaceutical
means of today. Chronic toxicity studies
must be undertaken to examine possible long-term
effects of cannabis use.*
Medical science must again confront the problems
of cannabis' insolubility in water and its variable
strength. Since human and animal responses
vary a great deal, individual doses must be titrated.
The popular "double blind" type of study methods
will require revision. The reporting of personal
drug experience was once acceptable to the scientific
community15S,22,25,29,34,39,44 Humans who are
drug "sophisticates" will again become indispensable
to psychoactive drug research, as wine tasters
are to the wine industry, for only humans can
verbally report the subtle and complex effects of
these substances.
Government agencies having stimulated little
significant clinical research in this field, the pharmaceutical
industry should take the initiative in
starting basic research and clinical studies into the
purified congeners of cannabis for their chemical
properties, pharmacologic qualities and therapeutic
applications.
Possible Therapeutic Applications of.
Tetrahydrocannabinols and Like Products
Analgesic-hypnoticl6 18,19,2 3,25,27,3 345
Appetite stimulant18'25'27
Antiepileptic-antispasmodic9,18,27.3 3,40,45
Prophylactic and treatment of the neuralgias, including
migraine and tic douloureux3"16'17"18'19'23'
25,28,31,3 3,38,40,45
Antidepressant-tranquillizer6,16.18,19,23,25,31,33,40,45
Anti-asthmatic 18,25,45
OXytoxic2I545
Antitussive 3.16,25,38,45
Topical anesthetic8
Withdrawal agent for opiate and alcohol addiction5
23'24'38'42'45
Childbirth analgesic12
Antibiotic7
Discussion
Medicine, being an empiric art, has not hesitated
in the past to utilize a substance first used for
recreational purposes,* in the pursuit of the more
noble purposes of healing, relieving pain and
teaching us more of the workings of the human
mind and body. The active constituents of cannabis
appear to have remarkably low acute and
chronic toxicity factors and might be quite useful
in the management of many chronic disease conditions.
More reasonable laws and regulations controlling
psychoactive drug research are required to
permit significant medical inquiry to begin so that
we can fill the large gaps in our knowledge of cannabis.
Diphenylhydantoin-Dilantin®
REFERENCES
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2. Ames, Frances: A dinical and metabolic study of acute intoxication
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3. Anderson, G. S. D.: Remarks on the remedial virtues of cannabis
indica, or Indian hemp, Boston Med. and Surg. J., 67:427-30,
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4. Bell, John: On the haschich or cannabis indica, Boston Med. and
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5. Birch, Edward A.: The use of Indian hemp in the treatment of
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6. Boyd, E. S., and Merritt, D. A.: Effects of a tetrahydrocannabinol
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8. Cunningham, D. D.: Report by Brigade-Surgeon-Lieut. Col.
D. D. Cunningham, F.R.S., C.I.E., on the nature of the effects accompanying
the continued treatment of animals with hemp drugs and
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9. Davis, J. P., and Ramsey, H. H.: Antiepileptic action of marihuana-
active substances, Federat. Proc., 8:284-85, Mar. 1949.
10. Dioscorides, Pedanius: The Greek Herbal of Dioscorides, Edited
by Robert T. Gunther, Hafner Publishing Co., New York, 1959, pp.
390-91.
11. Eddy, N. B., Halbach, H., Isbell, H., and Seevers, M. H.:
Drug dependence: its significance and characteristics. Psychopharmacology
Bull., 3:1-12, July 1966.
12. Effects of alcohol and cannabis during labor, JAMA, 94:1165,
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13. Goodman, L. S., and Gilman, A.: The Pharmacological Basis
of Therapeutics, 2nd Edition, Macmillan, New York, 1955.
14. Goodman, L. S., and Gilman, A.: The Pharmacological Basis
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15. Hamilton, H. C., Lescohier, A. W., and Perkins, R. A.: The
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16. Hare, Hobart Amory: Clinical and physiological notes on the
action of cannabis indica, Therap. Gaz., 11:225-28, 1887.
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20. Loewe, S.: The active principles of cannabis and the pharmacology
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21. Loewe, S.: Studies on the pharmacology and acute toxicity of
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22. Marshall, C. R.: A contribution to the pharmacology of
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the City of New York, Jaques Cattell, Lancaster, Pa., 1944.
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A MURMUR IN THE NECK
On a routine physical examination, you discover a patient has a murmur in his
neck, but no symptoms of vascular obstruction. What should you do?
"It has been my advice to take the murmur as evidence that the patient may
have atherosclerotic disease which could at some time affect his cerebral circulation.
I would put the man in my practice population, look after him fairly regularly,
and instruct him about possible future symptoms.
"If I picked up this sign in the hospital when the patient came in for a major
operation, I would feel justified in at least studying him arteriographically because
of the low mortality risk with arteriograms. If he has a great deal of obstruction,
and especially if I can squeeze out of him some past symptoms, I feel justified in
doing a prophylactic operation prior to the one for which he was admitted.
"The other position you could take, and I wouldn't argue too strongly against,
is that you do the arteriograms and be aware of what he has. In the event that
he does have a stroke during or after surgery, you'll know where the lesion is;
and if you get with it, chances are quite good he still would have a favorable
response. But in general my approach to the asymptomatic obstruction is conservative."
-E. STANLEY CRAWFORD, M.D., Houston
Extracted from Audio-Digest Internal Medicine,
Vol. 15, No. 19, in the Audio-Digest
Foundation's subscription series of taperecorded
programs.
Source: Marijuana In Medicine: Past Present And Future
about therapeutic properties of marijuana, or cannabis.
Analgesia, anticonvulsant action, appetite stimulation, ataraxia, antibiotic
properties and low toxicity were described throughout medical
literature, beginning in 1839, when O'Shaughnessy introduced cannabis
into the Western pharnacopoeia.
As these findings were reported throughout Western medicine, cannabis
attained wide use. Cannabis therapy was described in most pharmacopoeial
texts as a treatment for a variety of disease conditions.
During the second half of the 1800's and in the present century,
medical researchers in some measure corroborated the early reports
of the therapeutic potential of cannabis. In addition, much laboratory
research has been concerned with bioassay, determination of the mode
of action, and attempts to solve the problems of insolubility in water
and variability of strength among different cannabis specimens.
"Recreational" smoking of cannabis in the twentieth century and the
resultant restrictive federal legislation have functionally ended all medical
uses of marijuana.
In light of such assets as minimal toxicity, no buildup of tolerance,
no physical dependence, and minimal autonomic disturbance, immediate
major clinical reinvestigation of cannabis preparations is indicated
in the management of pain, chronic neurologic diseases, convulsive disorders,
migraine headache, anorexia, mental illness, and bacterial infections.
CANNABIS INDICA, CANNABIS sativa, Cannabis
americanus, Indian hemp and marijuana (or marihuana)
all refer to the same plant. Cannabis is used
throughout the world for diverse purposes and has
a long history characterized by usefulness, euphoria
or evil-depending on one's point of view.
To the agriculturist cannabis is a fiber crop; to
the physician of a century ago it was a valuable
medicine; to the physician of today it is an enigma;
to the user, a euphoriant; to the police, a menace;
to the traffickers, a source of profitable danger; to
the convict or parolee and his family, a source of
sorrow.
This paper is concerned primarily with the medicinal
aspects of cannabis.
Cannabis in Medicine Before 1800
The Chinese emperor Shen-nung is reported to
have taught his people to grow hemp for fiber in
the twenty-eighth century B.C. A text from the
period 1500-1200 B.C. documents a knowledge of
the plant in China-but not for use as fiber. In 200
A.D., the use of cannabis as an analgesic was described
by the physician Hoa-tho.44
In India the use of hemp preparations as a
remedy was described before 1000 B.C. In Persia,
cannabis was known several centuries before
Christ. In Assyria, about 650 B.C., its intoxicating
properties were noted."4
Except for Herodotus' report that the Scythians
used the smoke from burning hemp seeds for intoxication,
the ancient Greeks seemed to be unaware
of the psychoactive properties of cannabis.
Dioscorides in the first century A.D. rendered an
accurate morphologic description of the plant, but
made no note of intoxicating properties.10
In the thirteenth and fourteenth centuries,
Arabic writers described the social use of cannabis
and resultant cruel but unsuccessful attempts to
suppress its non-medical use.44
Although Galen described the use of the seeds
for creating warmth, he did not describe the intoxicating
qualities of hemp. Of interest is the paucity
of references to hemp's intoxicating properties in
the lay and medical literature of Europe before the
1 800'S.44
Cannabis in Nineteenth-Century Medicine
The therapeutic use of cannabis was introduced
into Western medicine in 1839, in a 40-page article
by W. B. O'Shaughnessy, a 30-year-old physician
serving with the British in India.27 His discussion
of the history of the use of cannabis products in the
East reveals an awareness that these drugs had not
only been used in medicine for therapeutic purposes,
but had also been used for recreational and
religious purposes.
O'Shaughnessy is not primarily known for his
discovery of hemp drugs, but rather for his basic
studies on intravenous electrolyte therapy in 1831,
and his introduction of the telegraph into India in
the 1850's.26
After studying the literature on cannabis and
conferring with contemporary Hindu and Mohammedan
wise men, O'Shaughnessy tested the effects
of various hemp preparations on animals, before
attempting to use them to treat humans. Satisfied
that the drug was reasonably safe, he administered
preparations of cannabis extract to patients, and
discovered that it had analgesic and sedative properties.
O'Shaughnessy successfully relieved the pain
of rheumatism and stilled the convulsions of an
infant with this strange new drug. His most spectacular
success came, however, when he quelled
the wrenching muscle spasms of tetanus and rabies
with the fragrant resin. Psychic effects resembling a
curious delirium, when an overdose was given,
were treated with strong purgatives, emetics with a
blister.to the nape of the neck, and leeches on the
temples.27
The use of cannabis derivatives for medicinal
purposes spread rapidly throughout Western medicine,
as is evidenced in the report of the Committee
on Cannabis Indica of the Ohio State Medical
Society, published in 1860. In that report physicians
told of success in treating stomach pain,
childbirth psychosis, chronic cough, and gonorrhea
with hemp products.25 A Dr. Fronmueller, of
Fuerth, Ohio, summarized his experiences with the
drug as follows:
I have used hemp many hundred times to
relieve local pains of an inflammatory as well
as neuralgic nature, and judging from these
experiments, I have to assign to the Indian
hemp a place among the so-called hypnotic
medicines next to opium; its effects are less
intense, and the secretions are not so much
suppressed by it. Digestion is not disturbed;
the appetite rather increased; sickness of the
stomach seldom induced; congestion never.
Hemp may consequently be employed in inflammatory
conditions. It disturbs the expectoration
far less than opium; the nervous
system is also not so much affected. The
whole effect of hemp being less violent, and
producing a more natural sleep, without interfering
with the actions of the internal organs,
it is certainly often preferable to opium, although
it is not equal to that drug in strength
and reliability. An alternating course of
opium and Indian hemp seems particularly
adapted to those cases where opium alone
fails in producing the desired effect.25
Because cannabis did not lead to physical dependence,
it was found to be superior to the opiates
for a number of therapeutic purposes. Birch, in
1889, reported success in treating opiate and
chloral addiction with cannabis,5 and Mattison in
1891 recommended its use to the young physician,
comparing it favorably with the opiates:
With a wish for speedy effect, it is so easy
to use that modern mischief-maker, hypodermic
morphia, that they [young physicians]
are prone to forget remote results of incautious
opiate giving.
Would that the wisdom which has come to
their professional fathers through, it may be,
a hapless experience, might serve them to
steer clear of narcotic shoals on which many
a patient has gone awreck.
Indian hemp is not here lauded as a specific.
It will, at times, fail. So do other drugs.
But the many cases in which it acts well, entitle
it to a large and lasting confidence.
My experience warrants this statement:
cannabis indica is, often, a safe and successful
anodyne and hypnotic.23
In their study of the medical applications of
cannabis, physicians of the nineteenth century repeatedly
encountered a number of difficulties. Recognizing
the therapeutic potential of the drug,
many experimenters sought ways of overcoming
these drawbacks to its use in medicine, in particular
the following:
Cannabis products are insoluble in water.
The onset of the effects of medicinal preparations
of cannabis takes an hour or so; its action is
therefore slower than that of many other drugs.
Different batches of cannabis derivatives vary
greatly in strength; moreover, the common procedure
for standardization of cannabis samples, by
administration to test animals, is subject to error
owing to variability of reactions among the animals.
There is wide variation among humans in their
individual responses to cannabis.
Despite these problems regarding the uncertainty
of potency and dosage and the difficulties in mode
of administration, cannabis has several important
advantages over other substances used as analgesics,
sedatives, and hypnotics:
The prolonged use of cannabis does not lead to
the development of physical dependence.1 '1,131424,
39,44
There is minimal development of tolerance to
cannabis products. * 11,13,14,24,44
Cannabis products have exceedingly low toxicity.
9.21'22'24 (The oral dose required to kill a
mouse has been found to be about 40,000 times the
dose required to produce typical symptoms of intoxication
in man.)21
Cannabis produces no disturbance of vegetative
functioning, whereas the opiates inhibit the gastrointestinal
tract, the flow of bile and the cough
reflex."2'24'44'46
Besides investigating the physical effects of
medicinal preparations of cannabis, nineteenth-century
physicians observed the psychic effects of the
drug in its therapeutic applications.4'27'33 They
found that cannabis first mildly stimulates, and
then sedates the higher centers of the brain. Hare
suggested in 1887 a possible mechanism of cannabis'
analgesic properties:
During the time that this remarkable drug
is relieving pain a very curious psychical condition
manifests itself; namely, that the diminution
of the pain seems to be due to its fading
away in the distance, so that the pain becomes
less and less, just as the pain in a delicate ear
would grow less and less as a beaten drum
was carried farther and farther out of the
range of hearing.
This condition is probably associated with
the other well-known symptom produced by
the drug; namely, the prolongation of time.16
Reynolds, in 1890,33 summed up 30 years of his
clinical experience using cannabis, finding it useful
as a nocturnal sedative in senile insomnia, and
valuable in treating dysmenorrhea, neuralgias including
tic douloureux and tabetic symptoms,
migraine headache and certain epileptoid or choreoid
muscle spasms. He felt it to be of uncertain
benefit in asthma, alcoholic delirium and depressions.
Reynolds thought cannabis to be of no value
in joint pains that were aggravated by motion and
in cases of true chronic epilepsy.
Reynolds stressed the necessity of titrating the
dose of each patient, increasing gradually every
third or fourth day, to avoid "toxic" effects:
The dose should be given in minimum
quantity, repeated in not less than four or six
hours, and gradually increased by one drop
every third or fourth day, until either relief
is obtained, or the drug is proved, in such
case, to be useless. With these precautions I
have never met with any toxic effects, and
have rarely failed to find, after a comparatively
short time, either the value or the uselessness
of the drug.33
Concerning migraine headache, Osler stated in
his text11: Cannabis indica is probably the most
satisfactory remedy.' 1,28
Cannabis in Twentieth-Century Medicine
In his definitive survey of the literature and report
of his own studies, deceptively titled Marihuana,
America's New Drug Problem, Walton
notes that cannabis was widely used during the latter
half of the nineteenth century, and particularly
before new drugs were developed:
This popularity of the hemp drugs can be
attributed partly to the fact that they were introduced
before the synthetic hypnotics and
analgesics. Chloral hydrate was not introduced
until 1869 and was followed in the
next 30 years by paraldehyde, sulfonal and
the barbitals. Antipyrine and acetanilide, the
first of their particular group of analgesics,
were introduced about 1884. For general
sedative and analgesic purposes, the only
drugs commonly used at this time were the
morphine derivatives and their disadvantages
were very well known. In fact, the most attractive
feature of the hemp narcotics was
probably the fact that they did not exhibit
certain of the notorious disadvantages of the
opiates. The hemp narcotics do not constipate
at all, they more often increase than decrease
appetite, they do not particularly depress the
respiratory center even in large doses, they
rarely or never cause pruritus or cutaneous
eruptions and, most important, the liability of
developing addiction is very much less than
with opiates.44
The use of cannabis in American medicine was
seriously affected by the increased use of opiates
in the latter half of the nineteenth century. With
the introduction of the hypodermic syringe into
American medicine from England in 1856 by Barker
and Ruppaner, the use of the faster acting,
water-soluble opiate drugs rapidly increased. The
Civil War helped to spread the use of opiates in
this country; the injected drugs were administered
widely-and often indiscriminately-to relieve the
pain of maimed soldiers returning from combat.
(Opiate addiction was once called the "army
disease".)41 As the use of injected opiates increased,
cannabis declined in popularity.
Cannabis preparations were still widely available
in legend and over-the-counter forms in the 1930's.
Crump* in 1931 mentioned the proprietaries
"Piso's Cure," "One Day Cough Cure" and "Neurosine"
as containing cannabis.44 In 1937 Sasman
listed 28 pharmaceuticals containing cannabis.36
Cannabis was still recognized as a medicinal agent
in that year, when the committee on legislative activities
of the American Medical Association concluded
as follows:
.. . there is positively no evidence to indicate
the abuse of cannabis as a medicinal
agent or to show that its medicinal use is leading
to the development of cannabis addiction.
Cannabis at the present time is slightly used
for medicinal purposes, but it would seem
worthwhile to maintain its status as a medicinal
agent for such purposes as it now has.
There is a possibility that a re-study of the
drug by modern means may show other advantages
to be derived from its medicinal
use.32
Meanwhile, in Mexico, the poor were smoking
marijuana to relax and to endure heat and fatigue.
(Originally Marijuana was the Mexican slang word
for the smoking preparation of dried leaves and
flowering tops of the Cannabis sativa plant-the
indigenous variety of the hemp plant.)
The recreational smoking of marijuana may
have started in this country in New Orleans in
about 1910, and continued on a small scale there
until 1926, when a newspaper ran a six-part series
on the use of the drug.44 The fad subsequently
spread up the Mississippi and throughout the
United States, faster than local and state laws
could be passed to discourage it. The use of "tea"
or "muggles" blossomed into a minor "psychedelic
revolution" of the 1930's. Narcotics officers encouraged
the enactment of local prohibitory laws
and eventually succeeded in bringing about restrictive
Federal legislation. In 1937 Congress passed
the Marihuana Tax Act, the finale to a series of
prohibitory acts in the individual states. Under the
new laws, the already dwindling use of cannabis
as a therapeutic substance in medicine was brought
to a virtual halt. In 1941, cannabis was dropped
from the National Formulary and Pharmacopoeia.
Around the time of the passage of the Marihuana
Tax Act, Walton postulated sites of action
for cannabis drugs. Cortical areas, he found, are
affected at low dosage, while at high dosage there
seems to be a depressant effect on the thalamocortical
pathways. Hyperemia of the brain appears
to be a local phenomenon, unless centers controlling
vasodilation might be located in the
thalamo-cortical region. Similar possible mechanisms
are suggested for the phenomenon of mild
hypoglycemia, usual hunger and thirst and occasional
lacrimation and nausea.44
Despite restrictive legislation, a few medical researchers
have had the opportunity to continue the
investigation of the therapeutic applications of cannabis
in recent years. In his study of the medical
applications of cannabis for Mayor LaGuardia's
committee, Dr. Samuel Allentuck reported, among
other findings, favorable results in treating withdrawal
of opiate addicts with tetrahydrocannabinol
(THC), a powerful purified product of the hemp
plant.1.24
An article in 1949, buried in a journal of chemical
abstracts, reported that a substance related to
THC controlled epileptic seizures in a group of
children more effectively than diphenylhydantoin
(Dilantin®), a most commonly prescribed anticonvulsant.
9
A number of experimenters, believing that cannabis
products might be of value in psychiatry,
have investigated the applications of various forms
of them in the treatment of mental disorders. Cannabis
had been used in the nineteenth century to
treat mental illness.19.25.45.46 However, aside from
some rather equivocal clinical studies, primarily in
the treatment of depression,29.30 35.39 and another
report of success in treating withdrawal from
alcohol and opiate addiction,42 no significant contemporary
psychiatric studies involving cannabis
therapy have been reported to date.
The Current Status of Cannabis Research
Many current "authoritative" publications unequivocally
state that there is no legitimate medical
use for marijuana. As compared with the
1800's, this century has seen very little medical
research on the array of some 20 chemicals that
are found in the hemp plant.37
Today's readers may tend to be skeptical about
a report of a cure for gonorrhea published over a
century ago.19.25 Such findings may bear reinvestigation,
however, in the light of a report from
Czechoslovakia in 1960 that cannabidiolic acid, a
product of the unripe hemp plant, has bacteriocidal
properties.7 Some of the therapeutic applications
reported in the early medical papers have been
corroborated by later investigators, but for the
most part the therapeutic aspects of cannabis remain
to be re-explored under modern clinical
conditions.
In the past 20 years, clinical and basic research
on cannabis have dwindled to practically nothing.
The record of tax stamps issued by the Federal
Bureau of Narcotics for cannabis research, as compared
with those for research on narcotic drugs,
tells the story of the 20-year "drought" in the investigation
of cannabis products: 43 Eleven studies funded by the National Institute
of Mental Health in 1967 concerning cannabis
were either specialized animal experiments, part of
an observational sociologic study of a number of
drugs, or explorations of chemical detection
methods.
The Future of Cannabis and Medicine
Unless existing restrictive state and Federal laws
governing marijuana are changed, there will be no
future for either modern scientific investigation or
controlled clinical trial by present-day methods.
A concerted effort is indicated for full-scale
investigations where knowledge is lacking. Acute
and chronic effects of cannabis should be restudied
by modern methods. Metabolic pathways of action
and detoxification need exploration by the pharmaceutical
means of today. Chronic toxicity studies
must be undertaken to examine possible long-term
effects of cannabis use.*
Medical science must again confront the problems
of cannabis' insolubility in water and its variable
strength. Since human and animal responses
vary a great deal, individual doses must be titrated.
The popular "double blind" type of study methods
will require revision. The reporting of personal
drug experience was once acceptable to the scientific
community15S,22,25,29,34,39,44 Humans who are
drug "sophisticates" will again become indispensable
to psychoactive drug research, as wine tasters
are to the wine industry, for only humans can
verbally report the subtle and complex effects of
these substances.
Government agencies having stimulated little
significant clinical research in this field, the pharmaceutical
industry should take the initiative in
starting basic research and clinical studies into the
purified congeners of cannabis for their chemical
properties, pharmacologic qualities and therapeutic
applications.
Possible Therapeutic Applications of.
Tetrahydrocannabinols and Like Products
Analgesic-hypnoticl6 18,19,2 3,25,27,3 345
Appetite stimulant18'25'27
Antiepileptic-antispasmodic9,18,27.3 3,40,45
Prophylactic and treatment of the neuralgias, including
migraine and tic douloureux3"16'17"18'19'23'
25,28,31,3 3,38,40,45
Antidepressant-tranquillizer6,16.18,19,23,25,31,33,40,45
Anti-asthmatic 18,25,45
OXytoxic2I545
Antitussive 3.16,25,38,45
Topical anesthetic8
Withdrawal agent for opiate and alcohol addiction5
23'24'38'42'45
Childbirth analgesic12
Antibiotic7
Discussion
Medicine, being an empiric art, has not hesitated
in the past to utilize a substance first used for
recreational purposes,* in the pursuit of the more
noble purposes of healing, relieving pain and
teaching us more of the workings of the human
mind and body. The active constituents of cannabis
appear to have remarkably low acute and
chronic toxicity factors and might be quite useful
in the management of many chronic disease conditions.
More reasonable laws and regulations controlling
psychoactive drug research are required to
permit significant medical inquiry to begin so that
we can fill the large gaps in our knowledge of cannabis.
Diphenylhydantoin-Dilantin®
REFERENCES
1. Adams, Roger: Marihuana, Bulletin of the New York Academy
of Medicine, 18:705-29, Nov. 1942.
2. Ames, Frances: A dinical and metabolic study of acute intoxication
with cannabis sativa and its role in the model psychoses, J. of
Mental Science, 104:972-99, Oct. 1958.
3. Anderson, G. S. D.: Remarks on the remedial virtues of cannabis
indica, or Indian hemp, Boston Med. and Surg. J., 67:427-30,
1863.
4. Bell, John: On the haschich or cannabis indica, Boston Med. and
Surg. J., 56:209-16, 229-36, 1857.
5. Birch, Edward A.: The use of Indian hemp in the treatment of
chronic chloral and chronic opium poisoning, Lancet, 1:625, 30 Mar.
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6. Boyd, E. S., and Merritt, D. A.: Effects of a tetrahydrocannabinol
derivative on some motor systems in the cat, Arch. Internat. de Pharmacodynamie
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7. CIBA Foundation Study Group, Hashish-Its Chemistry and
Pharmacology, 1964, pp. 45, 49.
8. Cunningham, D. D.: Report by Brigade-Surgeon-Lieut. Col.
D. D. Cunningham, F.R.S., C.I.E., on the nature of the effects accompanying
the continued treatment of animals with hemp drugs and
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9. Davis, J. P., and Ramsey, H. H.: Antiepileptic action of marihuana-
active substances, Federat. Proc., 8:284-85, Mar. 1949.
10. Dioscorides, Pedanius: The Greek Herbal of Dioscorides, Edited
by Robert T. Gunther, Hafner Publishing Co., New York, 1959, pp.
390-91.
11. Eddy, N. B., Halbach, H., Isbell, H., and Seevers, M. H.:
Drug dependence: its significance and characteristics. Psychopharmacology
Bull., 3:1-12, July 1966.
12. Effects of alcohol and cannabis during labor, JAMA, 94:1165,
1930.
13. Goodman, L. S., and Gilman, A.: The Pharmacological Basis
of Therapeutics, 2nd Edition, Macmillan, New York, 1955.
14. Goodman, L. S., and Gilman, A.: The Pharmacological Basis
of Therapeutics, 3d Edition, Macmillan, New York, 1965.
15. Hamilton, H. C., Lescohier, A. W., and Perkins, R. A.: The
hysiological activity of cannabis sativa. Comparison of extracts from
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Pharm. Assoc., 2:22-30, 1913.
16. Hare, Hobart Amory: Clinical and physiological notes on the
action of cannabis indica, Therap. Gaz., 11:225-28, 1887.
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Lee Brothers and Co., Philadelphia, 1892, Vol. 3.
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Book Depot, Bombay, 1954.
19. Lilly's Hand Book of Pharmacy and Therapeutics, Eli Lilly
and Co., Indianapolis, 1898, p. 32.
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of the cannabinols, Archiv fur Experim. Pathologie und
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St. Louis Med. and Surg. J., 61:265-71, Nov. 1891.
24. Mayor's Committee on Marihuana, The Marihuana Problem in
the City of New York, Jaques Cattell, Lancaster, Pa., 1944.
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Prom Transactions of the Fifteenth Annual Meeting of the Ohio State
Medical Society, Follett, Foster and Co., Columbus, Ohio, 1860, pp.
75-100.
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Eng. J. of Med., 276:283-84, 2 Feb. 1967.
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hemp, or gunjah, Trans. Med. and Phy. Soc., Bengal, 71-102, 1838-
40; 421-61, 1842.
28. Osler, W., and McCrae, T.: Principles and practice of Medicine,
8th Edition, D. Appleton and Co., New York, 1916, p. 1089.
29. Parker, C. S., and Wrigley, F.: Synthetic cannabis preparations
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35. Rolls, E. J., and Stafford-Clark, D.: Depersonalization treated
by cannabis indica and psychotherapy, Guy's Hospital Report,
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N.J. Med Soc., 35:51-52, Jan. 1938.
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A MURMUR IN THE NECK
On a routine physical examination, you discover a patient has a murmur in his
neck, but no symptoms of vascular obstruction. What should you do?
"It has been my advice to take the murmur as evidence that the patient may
have atherosclerotic disease which could at some time affect his cerebral circulation.
I would put the man in my practice population, look after him fairly regularly,
and instruct him about possible future symptoms.
"If I picked up this sign in the hospital when the patient came in for a major
operation, I would feel justified in at least studying him arteriographically because
of the low mortality risk with arteriograms. If he has a great deal of obstruction,
and especially if I can squeeze out of him some past symptoms, I feel justified in
doing a prophylactic operation prior to the one for which he was admitted.
"The other position you could take, and I wouldn't argue too strongly against,
is that you do the arteriograms and be aware of what he has. In the event that
he does have a stroke during or after surgery, you'll know where the lesion is;
and if you get with it, chances are quite good he still would have a favorable
response. But in general my approach to the asymptomatic obstruction is conservative."
-E. STANLEY CRAWFORD, M.D., Houston
Extracted from Audio-Digest Internal Medicine,
Vol. 15, No. 19, in the Audio-Digest
Foundation's subscription series of taperecorded
programs.
Source: Marijuana In Medicine: Past Present And Future
